Chen Yuk-Kwan, Hsue Shui-Sang, Lin Li-Min
Department of Oral Pathology, School of Dentistry, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan.
Head Neck. 2004 Nov;26(11):945-52. doi: 10.1002/hed.20098.
TP73, a p53 homologue gene, shares similar structural sequences with p53. The aim of this study was to investigate the p73 expression for human buccal epithelial dysplasia (ED) and squamous cell carcinoma (SCC).
Seventy-five samples of human buccal ED, including mild, moderate, and severe ED (25 samples in each category), were analyzed for p73 protein expression by means of immunohistochemistry. Twenty-five samples of human buccal SCCs were analyzed for p73 mRNA expression with reverse transcription-polymerase chain reaction (RT-PCR) and were also analyzed for protein expression with immunohistochemical analysis.
By use of immunohistochemical analysis, nuclear staining of p73 protein was detected in a subset of normal mucosa, buccal ED, and SCC specimens. p73 nuclear staining was noted for the basal cells of normal buccal mucosa. For buccal lesions deriving from mild, moderate, and severe ED, p73 protein was observed in basal and parabasal layers and in more superficial cell layers corresponding to the spinous layer. For well-differentiated carcinomas, p73 immunoreactivity was chiefly observed among the less-differentiated cells in the periphery of carcinomatous clusters, whereas moderately differentiated carcinomas revealed homogeneous staining, involving nearly all of the tumor cells. On RT-PCR, the expression of p73 mRNA from buccal SCC was noted to be compatible with the findings of immunohistochemical analysis. An electrophoretic band with a 180-bp PCR product corresponding to p73 mRNA has been observed. The expression of p73 seemed to be significantly elevated for specimens of buccal ED (protein level) and SCC (protein and mRNA levels) compared with the analogous expression for normal control tissue (Fisher's exact test, p <.001). Also, p73 expression (protein and mRNA levels) correlated significantly with cervical lymph node metastasis for cases of buccal SCC (Fisher's exact test, p <.001). Eight cases of ED (protein level) showing p73 positivity have undergone malignant transformation to develop SCCs in 2 years follow-up, but no statistical significance was established (Fisher's exact test, p >.05).
The data suggest that p73 expression may be (1) associated with the differentiation of oral stratified squamous epithelium, (2) an early event in human oral carcinogenesis, and (3) associated with the nodal status of patients with oral carcinoma and a possible indicator for malignant change of oral ED.
TP73是一种p53同源基因,与p53具有相似的结构序列。本研究旨在调查人颊黏膜上皮发育异常(ED)和鳞状细胞癌(SCC)中p73的表达情况。
采用免疫组织化学方法分析75例人颊黏膜ED样本,包括轻度、中度和重度ED(各25例)中p73蛋白的表达。采用逆转录聚合酶链反应(RT-PCR)分析25例人颊黏膜SCC样本中p73 mRNA的表达,并采用免疫组织化学分析其蛋白表达。
通过免疫组织化学分析,在部分正常黏膜、颊黏膜ED和SCC标本中检测到p73蛋白的核染色。在正常颊黏膜的基底细胞中发现p73核染色。对于源自轻度、中度和重度ED的颊黏膜病变,在基底和副基底层以及对应棘层的更表层细胞中观察到p73蛋白。对于高分化癌,p73免疫反应主要在癌巢周边分化较差的细胞中观察到,而中分化癌则显示均匀染色,几乎涉及所有肿瘤细胞。RT-PCR结果显示,颊黏膜SCC中p73 mRNA的表达与免疫组织化学分析结果一致。观察到一条对应p73 mRNA的180 bp PCR产物的电泳条带。与正常对照组织的类似表达相比,颊黏膜ED(蛋白水平)和SCC(蛋白和mRNA水平)标本中p73的表达似乎显著升高(Fisher精确检验,p <.001)。此外,颊黏膜SCC病例中p73的表达(蛋白和mRNA水平)与颈部淋巴结转移显著相关(Fisher精确检验,p <.001)。8例p73蛋白表达阳性的ED病例在2年随访中发生恶变发展为SCC,但未发现统计学意义(Fisher精确检验,p >.05)。
数据表明,p73表达可能(1)与口腔复层鳞状上皮的分化相关,(2)是人类口腔癌变的早期事件,(3)与口腔癌患者的淋巴结状态相关,可能是口腔ED恶变的一个指标。